Arthritis is predominantly a disease of the elderly and morbidity has increased with civilization. The treatment of arthritis includes administration of corticosteroids to eliminate inflammatory symptoms and inhibit the immune system, or administration of non-steroid anti-inflammatory drugs (NSAIDs), such as COX-1 inhibitors, COX-2 inhibitors, Celebrex or Ibuprofen, to ameliorate pain and inflammation. However, severe side effects and limited effects of these drugs drive new-generation of drugs to be developed.
The new-generation of drugs for the treatment of arthritis focus on the role of the cytokine, TNF-α, during the development of arthritis. A series of bioagents to decrease the secretion of TNF-α in arthritis patients has been developed, like the anti-TNF-α antibody, Adalimumab and Infliximab, or TNF-α antagonist, Etanercept. Studies show that a combination of an immunoinhibitory agent, methotrexate, and the TNF-α antagonist, etanercept, may increase the treatment effect of arthritis (Tracey D, et al., Tumor necrosis factor antagonist mechanisms of action: a comprehensive review, Pharmacology & Therapeutics 117 (2008) 244˜279.). The agents for inhibition of other cytokines, such as IL-6 antibodies and IL-β-ra, have also been known for the treatment of arthritis. However, the limited efficacy, side effects and single administration present in these agents has lead to an urgent desire to develop new drugs.